The present invention is concerned with a novel process for making racemic and optically active 3-amino-pyrrolidine derivatives and with the use of this process in making cephalosporin derivatives.
3-Amino-pyrrolidine derivatives, especially optically active 3-amino-pyrrolidine derivatives, are important intermediates for the production of agrochemicals and of pharmaceutically active substances such as, for example, of vinylpyrrolidinone-cephalosporin derivatives.
3-Amino-pyrrolidine derivatives can be made by known methods, for example as described in EP-A 0 218 249 starting from 1,2,4-trisubstituted butane derivatives such as e.g. tribromobutane or trihydroxybutane. The racemic derivatives can then, if desired, can be converted by a racemate resolution into optically active 3-amino-pyrrolidine derivatives as described in, JP 09124595-A. A process for the manufacture of optically active 3-amino-pyrrolidine derivatives based on the conversion of 4-hydroxy-proline as described, for example, in J. Med. Chem. 1764(92), 35, gives optically active 3-aminopyrrolidine over 3 steps.
The known methods for making 3-aminopyrrolidine derivatives as described, for example, in UK Patent No. 1 392 194, EP 0 391 169 and U.S. Pat. No. 4 916 141, are time consuming and lead to expensive intermediates. The interest in other processes for making 3-amino-pyrrolidine derivatives, especially of optically active 3-amino-pyrrolidine derivatives, is therefore extremely high. It has now been found that 3-amino-pyrrolidine derivatives, especially optically active 3-amino-pyrrolidine derivatives, can be made in high yields in a simple manner from 1,2,4-trihydroxybutane derivatives.